NaHMDS

Sterically hindered amines often tend to form ureas with (BOC)20, because of isocyanate formation. The problem can be avoided by reacting the amine with NaHMDS and then with (BOC)20. The isocyanates can also be converted to the BOC group by heating with r-BuOH. When other alcohols are used, the corresponding carbamate is produced. ... 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles in THE or 5% MeCN/THF afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-2H- and 2-aryl-4-imino-6,7,8,9-terahydro-4//-pyrido[l,2-n]pyrimidines in 70-98% and 2-30% yields, respectively (00OL3389). When the reactions were carried out in the presence of 2 equiv of NaHMDS the product ratio was reversed. 

Oxidation of the sodium enolate of 15b, prepared by using NaHMDS, with ( )-2-phenylsulfonyl-3-phenyloxaziridine yielded the desired 7-hydroxy derivative 23 (R = H) and its C(7) epimer with a very low... 

Scheme 9 Total synthesis of petrosins C (98) and D (99) [40], Experimental conditions i. PhS02CH2Cl, NaOH, DMSO ii. NaOMe, MeOH, rt Hi. (a) -BuLi, THE (b) (Z)-CICH2CH = CHCH2OTBS iv. 5% Na/Hg, MeOH v. (a) -BuLi, THE (b) TBOS replaced by chloride in 104 vi. (a) -BuLi, THE (b) MgBr2-Et20 (c) PhSSPh vii. (NH4)6Mo7024, H2O2 via. IN HCl, THE ix. MsCl, LiCl, 2,6-lutidine, DMF x. NaHMDS, THE xi. p-TSNHNH2, NaOAc, THE, H2O xii. (a) 3 eq. w-BuLi, 2,6-lutidine, THE (b) CH2 = CHCH2I xiii. Na/Hg, THE, MeOH xiv. (a) s-BuLi, TMEDA, ether, (b) CH2 = CHCH2Br...

Scheme 1.1 shows data for the regioselectivity of enolate formation for several ketones under various reaction conditions. A consistent relationship is found in these and related data. Conditions of kinetic control usually favor formation of the less-substituted enolate, especially for methyl ketones. The main reason for this result is that removal of a less hindered hydrogen is faster, for steric reasons, than removal of a more hindered hydrogen. Steric factors in ketone deprotonation are accentuated by using bulky bases. The most widely used bases are LDA, LiHMDS, and NaHMDS. Still more hindered disilylamides such as hexaethyldisilylamide9 and bis-(dimethylphenylsilyl)amide10 may be useful for specific cases. 

One of the compounds shown below undergoes intramolecular cyclization to give a tricyclic ketone on being treated with NaHMDS, but the other does not cyclize. Indicate which compound will cyclize more readily and offer and explanation. 

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-22/-pyrido[l,2- ]pyrimidines <20000L3389, 2002W002/00629>. The minor isomers, 2-aryl-4-imino-6,7,8,9-tetrahy-dro-4/7-pyrido[l,2- ]pyrimidines could also be isolated in 2-30% yields from the reaction mixtures <20000L3389>. When the reactions were carried out in the presence of 2 equiv of NaHMDS, the product ratio was reversed. From the reaction mixture of 2-aminopyridine and perfluoro-2-methylpent-2-ene in MeCN, a 9 1 mixture of 2,4-difluoro-2-pentafluoroethyl-3-trifluoromethyl-477- and the isomeric 2,4-difluoro-4-pentafluoroethyl-3-trifluoromethyl-277-pyr-ido[l,2- ]pyrimidine (64%), and 2-pentafluoroethyl-3-trifluoromethyl-47/-pyrido[l,2- ]-pyrimidine-4-one (20%) was isolated <2000JFC(103)105>. 

A mild and efficient a-heteroarylation of simple esters and amides via nucleophilic aromatic substitution has been described <06OL1447>. Treatment of 2-chloro-benzo[//Jthiazole 99 with tert-butyl propionate in the presence of NaHMDS under nitrogen furnishes tert-butyl 2-(benzo[c(jthiazol-2-yl)propanoate 100. When the same reaction is preformed initially under nitrogen and then exposed to air, the hydroxylation product 101 is obtained. This method offers two desirable features that are either complementary or improvements to the palladium-catalyzed a-arylation reactions. First, heteroaryl chlorides... 

A highly stereoselective synthesis of the (3-substituted P-amino sulfone 271 involves the addition of a sulfonyl anion, derived from A-PMB sultam 268 upon treatment with NaHMDS, to chiral A-sulfinyl imine (5)-269 <06OL789>. Removal of the A-sulfinyl followed by basic workup affords amine 271. The stereochemical outcome of the adduct 270 was established via proton NMR analysis of the Mosher s amide derived from 271. 

A practical a-heteroarylation of simple esters or amides has been developed via nucleophilic aromatic substitution. Exposure of chlorothiadiazoles 317 and 319 to NaHMDS and tert-butyl acetate or iV-dimethylacetamide leads to the formation of functionalized... 

Nucleophilic reactions at the carbon atoms of 1,3,4-thiadiazoles occur readily owing to the electron-deficient nature of this ring. Halo-substituted thiadiazoles are therefore highly activated and react with a wide range of nucleophiles. Carbon-based nucleophiles such as malonates have been used in the synthesis of 2-substituted thiadiazoles. When chlorothiadiazole 52 was treated with ethyl acetate in the presence of NaHMDS, the 2-phenyl-1,3,4-thiadiazol-5-ylacetic ester 53 was obtained (Equation 6) <20060L1447>. 

---